Forkhead box gene transcriptions

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Associate Editor(s)-in-Chief: Henry A. Hoff

"Forkhead box (Fox) proteins are a superfamily of evolutionarily conserved transcriptional regulators, which control a wide spectrum of biological processes."[1]

"Forkhead box (FOX) proteins comprise a large family of transcription factors (TFs), members of which display functional diversity and participate in cellular processes ranging from development to immunity and metabolism1–2. More than 170 FOX family members have been identified from different species and classified into 19 subfamilies (from FOXA to FOXS)3–4."[2]

Human genes

Main article: TATA box forkhead family

Gene ID: 2308 is FOXO1 forkhead box O1 on 13q14.11.

Interactions

Consensus sequences

"FOXA2, a member of the forkhead family of transcription factors, plays essential roles in liver development and bile acid homeostasis. [We] report a 2.8 Å co-crystal structure of the FOXA2 DNA-binding domain (FOXA2-DBD) bound to a DNA duplex containing a forkhead consensus binding site (GTAAACA)."[2]

"Most paralogous FOX proteins bind to the canonical DNA response element 5′-RYAAAYA-3′ (R = A or G, Y = C or T)11–13."[2]

"Genome-wide analysis of FOXA2-binding sites by ChIP-seq in human and mouse adult liver tissues suggested that FOXA2 binds to the consensus sequence (5′-GTAAACA-3′) of the FOX family24–25."[2]

"Forkhead box protein O1 (FOXO1), a master transcriptional factor for gluconeogenesis in the liver, directly regulates TXNIP expression through the binding of the promoter region of TXNIP which contains a conserved consensus sequence, ′GTAAACAA′, of the FOXO binding site [100,101]."[3]

Hypotheses

Main article: Hypotheses
  1. A1BG has no forkhead boxes in either promoter.
  2. A1BG is not transcribed by a forkhead box.
  3. A forkhead box does not participate in the transcription of A1BG.

Forkhead box (Yoshihara) samplings

Copying a responsive elements consensus sequence GTAAACAA and putting the sequence in "⌘F" finds none between ZNF497 and A1BG or none between ZSCAN22 and A1BG as can be found by the computer programs.

For the Basic programs testing consensus sequence GTAAACAA (starting with SuccessablesFboxY.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:

  1. negative strand, negative direction: 0.
  2. positive strand, negative direction: 0.
  3. negative strand, positive direction: 0.
  4. positive strand, positive direction: 0.
  5. inverse complement, negative strand, negative direction: 0.
  6. inverse complement, positive strand, negative direction: 0.
  7. inverse complement, negative strand, positive direction: 0.
  8. inverse complement, positive strand, positive direction: 0.

Forkhead box (Li) samplings

Copying an apparent consensus sequence of (A/G)(C/T)AAA(C/T)A and putting it in "⌘F" finds none located between ZSCAN22 and A1BG and none between ZNF497 and A1BG as can be found by the computer programs.

For the Basic programs testing consensus sequence (A/G)(C/T)AAA(C/T)A (starting with SuccessablesFork.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:

  1. negative strand, negative direction, looking for (A/G)(C/T)AAA(C/T)A, 1, GTAAATA at 4536.
  2. positive strand, negative direction, looking for (A/G)(C/T)AAA(C/T)A, 9, ATAAATA at 4074, ATAAACA at 3337, ACAAATA at 3333, ATAAACA at 2876, ACAAACA at 2512, ACAAACA at 2487, GCAAACA at 2483, GCAAACA at 1539, ACAAACA at 1391.
  3. negative strand, positive direction, looking for (A/G)(C/T)AAA(C/T)A, 1, ACAAACA at 4256.
  4. positive strand, positive direction, looking for (A/G)(C/T)AAA(C/T)A, 1, ACAAATA at 2346.
  5. inverse complement, negative strand, negative direction, looking for T(A/G)TTT(A/G)(C/T), 10, TATTTAT at 4074, TATTTGG at 3364, TATTTGT at 3337, TGTTTAT at 3333, TATTTGA at 3016, TATTTGT at 2876, TGTTTGT at 2512, TGTTTGT at 2487, TGTTTGG at 1588, TGTTTGT at 1391.
  6. inverse complement, positive strand, negative direction, looking for T(A/G)TTT(A/G)(C/T), 0.
  7. inverse complement, negative strand, positive direction, looking for T(A/G)TTT(A/G)(C/T), 2, TGTTTGC at 3340, TGTTTAT at 2346.
  8. inverse complement, positive strand, positive direction, looking for T(A/G)TTT(A/G)(C/T), 2, TGTTTGT at 4256, TATTTAC at 3429.

Fork (4560-2846) UTRs

  1. Negative strand, negative direction: GTAAATA at 4536.
  2. Negative strand, negative direction: TATTTGG at 3364, TATTTGA at 3016.
  3. Positive strand, negative direction: ATAAATA at 4074, ATAAACA at 3337, ACAAATA at 3333, ATAAACA at 2876.

Fork positive direction (4265-4050) proximal promoters

  1. Negative strand, positive direction: ACAAACA at 4256.

Fork negative direction (2596-1) distal promoters

  1. Negative strand, negative direction: TGTTTGT at 2512, TGTTTGT at 2487, TGTTTGG at 1588, TGTTTGT at 1391.
  2. Positive strand, negative direction: GCAAACA at 2483, GCAAACA at 1539, ACAAACA at 1391.

Fork positive direction (4050-1) distal promoters

  1. Negative strand, positive direction: TGTTTGC at 3340, TGTTTAT at 2346.
  2. Positive strand, positive direction: TATTTAC at 3429.

Forkhead box random dataset samplings

  1. Forkr0: 8, ACAAACA at 3652, ACAAATA at 1789, ACAAATA at 1706, ATAAATA at 1496, ACAAATA at 505, ATAAACA at 501, GTAAACA at 402, GCAAATA at 143.
  2. Forkr1: 0.
  3. Forkr2: 1, ATAAACA at 4532.
  4. Forkr3: 1, GTAAACA at 1815.
  5. Forkr4: 1, GCAAACA at 693.
  6. Forkr5: 1, ATAAATA at 3046.
  7. Forkr6: 1, GTAAATA at 2371.
  8. Forkr7: 4, ACAAACA at 3786, ATAAATA at 3631, GCAAACA at 2896, GCAAATA at 661.
  9. Forkr8: 4, GTAAATA at 4553, ATAAATA at 4523, GTAAACA at 2895, ACAAACA at 2655.
  10. Forkr9: 6, GCAAACA at 4118, ATAAACA at 3938, ACAAACA at 3458, GTAAACA at 2384, ACAAATA at 2094, ACAAACA at 1094.
  11. Forkr0ci: 4, TATTTGA at 4230, TGTTTGA at 4181, TATTTGT at 3312, TATTTGG at 1644.
  12. Forkr1ci: 3, TATTTAG at 3612, TATTTAT at 3097, TGTTTAA at 973.
  13. Forkr2ci: 6, TATTTGG at 4415, TATTTGC at 4074, TATTTAC at 3618, TATTTGA at 1888, TGTTTGC at 1298, TATTTGT at 1120.
  14. Forkr3ci: 6, TGTTTAG at 4499, TGTTTGT at 2268, TGTTTAT at 769, TGTTTAA at 533, TGTTTGT at 451, TGTTTAG at 338.
  15. Forkr4ci: 4, TATTTAA at 3724, TGTTTAA at 2439, TGTTTAA at 704, TGTTTGG at 429.
  16. Forkr5ci: 7, TATTTAA at 3630, TGTTTAA at 2657, TATTTAC at 2631, TATTTAA at 1314, TATTTAT at 857, TGTTTAC at 717, TGTTTAA at 428.
  17. Forkr6ci: 9, TATTTAC at 4373, TGTTTGT at 4363, TATTTGA at 3859, TATTTGA at 2022, TATTTAG at 1145, TATTTAT at 1141, TATTTAT at 917, TGTTTGT at 911, TATTTAC at 188.
  18. Forkr7ci: 5, TATTTGT at 4225, TATTTAA at 2979, TGTTTAT at 2451, TATTTGA at 1810, TATTTAA at 331.
  19. Forkr8ci: 6, TATTTGG at 4311, TATTTGG at 2333, TGTTTGC at 1232, TATTTAC at 829, TATTTGG at 268, TGTTTGC at 46.
  20. Forkr9ci: 10, TGTTTAA at 3415, TGTTTAG at 3351, TATTTGA at 3331, TGTTTAC at 3170, TGTTTAC at 2250, TATTTAG at 969, TATTTAA at 810, TATTTAC at 624, TGTTTAA at 234, TGTTTGT at 22.

Forkr arbitrary (evens) (4560-2846) UTRs

  1. Forkr0: ACAAACA at 3652.
  2. Forkr2: ATAAACA at 4532.
  3. Forkr8: GTAAATA at 4553, ATAAATA at 4523, GTAAACA at 2895.
  4. Forkr0ci: TATTTGA at 4230, TGTTTGA at 4181, TATTTGT at 3312.
  5. Forkr2ci: TATTTGG at 4415, TATTTGC at 4074, TATTTAC at 3618.
  6. Forkr6ci: TATTTAC at 4373, TGTTTGT at 4363, TATTTGA at 3859.
  7. Forkr8ci: TATTTGG at 4311.

Forkr alternate (odds) (4560-2846) UTRs

  1. Forkr5: ATAAATA at 3046.
  2. Forkr7: ACAAACA at 3786, ATAAATA at 3631, GCAAACA at 2896.
  3. Forkr9: GCAAACA at 4118, ATAAACA at 3938, ACAAACA at 3458.
  4. Forkr1ci: TATTTAG at 3612, TATTTAT at 3097.
  5. Forkr3ci: TGTTTAG at 4499.
  6. Forkr5ci: TATTTAA at 3630.
  7. Forkr7ci: TATTTGT at 4225, TATTTAA at 2979.
  8. Forkr9ci: TGTTTAA at 3415, TGTTTAG at 3351, TATTTGA at 3331, TGTTTAC at 3170.

Forkr arbitrary negative direction (evens) (2846-2811) core promoters

  1. Forkr6: GTAAATA at 2371.

Forkr alternate positive direction (evens) (4445-4265) core promoters

  1. Forkr2ci: TATTTGG at 4415.
  2. Forkr6ci: TATTTAC at 4373, TGTTTGT at 4363.
  3. Forkr8ci: TATTTGG at 4311.

Forkr arbitrary negative direction (evens) (2811-2596) proximal promoters

  1. Forkr8: ACAAACA at 2655.

Forkr alternate negative direction (odds) (2811-2596) proximal promoters

  1. Forkr5ci: TGTTTAA at 2657, TATTTAC at 2631.

Forkr arbitrary positive direction (odds) (4265-4050) proximal promoters

  1. Forkr9: GCAAACA at 4118.
  2. Forkr7ci: TATTTGT at 4225.

Forkr alternate positive direction (evens) (4265-4050) proximal promoters

  1. Forkr0ci: TATTTGA at 4230, TGTTTGA at 4181.
  2. Forkr2ci: TATTTGC at 4074.

Forkr arbitrary negative direction (evens) (2596-1) distal promoters

  1. Forkr0: ACAAATA at 1789, ACAAATA at 1706, ATAAATA at 1496, ACAAATA at 505, ATAAACA at 501, GTAAACA at 402, GCAAATA at 143.
  2. Forkr4: GCAAACA at 693.
  3. Forkr6: GTAAATA at 2371.
  4. Forkr0ci: TATTTGG at 1644.
  5. Forkr2ci: TATTTGA at 1888, TGTTTGC at 1298, TATTTGT at 1120.
  6. Forkr4ci: TGTTTAA at 2439, TGTTTAA at 704, TGTTTGG at 429.
  7. Forkr6ci: TATTTGA at 2022, TATTTAG at 1145, TATTTAT at 1141, TATTTAT at 917, TGTTTGT at 911, TATTTAC at 188.
  8. Forkr8ci: TATTTGG at 2333, TGTTTGC at 1232, TATTTAC at 829, TATTTGG at 268, TGTTTGC at 46.

Forkr alternate negative direction (odds) (2596-1) distal promoters

  1. Forkr3: GTAAACA at 1815.
  2. Forkr7: GCAAATA at 661.
  3. Forkr9: GTAAACA at 2384, ACAAATA at 2094, ACAAACA at 1094.
  4. Forkr1ci: TGTTTAA at 973.
  5. Forkr3ci: TGTTTGT at 2268, TGTTTAT at 769, TGTTTAA at 533, TGTTTGT at 451, TGTTTAG at 338.
  6. Forkr5ci: TATTTAA at 1314, TATTTAT at 857, TGTTTAC at 717, TGTTTAA at 428.
  7. Forkr7ci: TGTTTAT at 2451, TATTTGA at 1810, TATTTAA at 331.
  8. Forkr9ci: TGTTTAC at 2250, TATTTAG at 969, TATTTAA at 810, TATTTAC at 624, TGTTTAA at 234, TGTTTGT at 22.

Forkr arbitrary positive direction (odds) (4050-1) distal promoters

  1. Forkr3: GTAAACA at 1815.
  2. Forkr5: ATAAATA at 3046.
  3. Forkr7: ACAAACA at 3786, ATAAATA at 3631, GCAAACA at 2896, GCAAATA at 661.
  4. Forkr9: ATAAACA at 3938, ACAAACA at 3458, GTAAACA at 2384, ACAAATA at 2094, ACAAACA at 1094.
  5. Forkr1ci: TATTTAG at 3612, TATTTAT at 3097, TGTTTAA at 973.
  6. Forkr3ci: TGTTTGT at 2268, TGTTTAT at 769, TGTTTAA at 533, TGTTTGT at 451, TGTTTAG at 338.
  7. Forkr5ci: TATTTAA at 3630, TGTTTAA at 2657, TATTTAC at 2631, TATTTAA at 1314, TATTTAT at 857, TGTTTAC at 717, TGTTTAA at 428.
  8. Forkr7ci: TATTTAA at 2979, TGTTTAT at 2451, TATTTGA at 1810, TATTTAA at 331.
  9. Forkr9ci: TGTTTAA at 3415, TGTTTAG at 3351, TATTTGA at 3331, TGTTTAC at 3170, TGTTTAC at 2250, TATTTAG at 969, TATTTAA at 810, TATTTAC at 624, TGTTTAA at 234, TGTTTGT at 22.

Forkr alternate positive direction (evens) (4050-1) distal promoters

  1. Forkr0: ACAAACA at 3652, ACAAATA at 1789, ACAAATA at 1706, ATAAATA at 1496, ACAAATA at 505, ATAAACA at 501, GTAAACA at 402, GCAAATA at 143.
  2. Forkr4: GCAAACA at 693.
  3. Forkr6: GTAAATA at 2371.
  4. Forkr8: GTAAACA at 2895, ACAAACA at 2655.
  5. Forkr0ci: TATTTGT at 3312, TATTTGG at 1644.
  6. Forkr2ci: TATTTAC at 3618, TATTTGA at 1888, TGTTTGC at 1298, TATTTGT at 1120.
  7. Forkr4ci: TATTTAA at 3724, TGTTTAA at 2439, TGTTTAA at 704, TGTTTGG at 429.
  8. Forkr6ci: TATTTGA at 3859, TATTTGA at 2022, TATTTAG at 1145, TATTTAT at 1141, TATTTAT at 917, TGTTTGT at 911, TATTTAC at 188.
  9. Forkr8ci: TATTTGG at 2333, TGTTTGC at 1232, TATTTAC at 829, TATTTGG at 268, TGTTTGC at 46.

Forkhead box analysis and results

Main article: Complex locus A1BG and ZNF497 § Forkhead boxes

"Most paralogous FOX proteins bind to the canonical DNA response element 5′-RYAAAYA-3′ (R = A or G, Y = C or T)11–13."[2]

Reals or randoms Promoters direction Numbers Strands Occurrences Averages (± 0.1)
Reals UTR negative 7 2 3.5 3.5
Randoms UTR arbitrary negative 15 10 1.5 1.6
Randoms UTR alternate negative 17 10 1.7 1.6
Reals Core negative 0 2 0 0
Randoms Core arbitrary negative 1 10 0.1 0.05
Randoms Core alternate negative 0 10 0 0.05
Reals Core positive 0 2 0 0
Randoms Core arbitrary positive 0 10 0 0.25
Randoms Core alternate positive 5 10 0.5 0.25
Reals Proximal negative 0 2 0 0
Randoms Proximal arbitrary negative 1 10 0.1 0.15
Randoms Proximal alternate negative 2 10 0.2 0.15
Reals Proximal positive 1 2 0.5 0.5
Randoms Proximal arbitrary positive 2 10 0.2 0.25
Randoms Proximal alternate positive 3 10 0.3 0.25
Reals Distal negative 7 2 3.5 3.5 ± 0.5 (--4,+-3)
Randoms Distal arbitrary negative 27 10 2.7 2.55
Randoms Distal alternate negative 24 10 2.4 2.55
Reals Distal positive 3 2 1.5 1.5 ± 0.5
Randoms Distal arbitrary positive 40 10 4.0 3.75
Randoms Distal alternate positive 34 10 3.4 3.75

Comparison:

The occurrences of real forkhead box UTRs, proximals, negative distals are greater than the randoms, positive distals are less than the randoms. This suggests that the real forkhead boxes are likely active or activable.

Diseases

The "deregulation of Fox family transcription factors has a crucial role in the development and progression of cancer".[1]

See also

References

  1. ↑ 1.0 1.1 Stephen S. Myatt; Eric W. -F. Lam (November 2007). "The emerging roles of forkhead box (Fox) proteins in cancer". Nature Reviews Cancer. 7: 847–859. doi:10.1038/nrc2223. Retrieved 2017-02-13.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 Jun Li, Ana Carolina Dantas Machado, Ming Guo, Jared M. Sagendorf, Zhan Zhou, Longying Jiang, Xiaojuan Chen, Daichao Wu, Lingzhi Qu, Zhuchu Chen, Lin Chen, Remo Rohs, and Yongheng Chen (25 July 2017). "Structure of the forkhead domain of FOXA2 bound to a complete DNA consensus site". Biochemistry. 56 (29): 3745–3753. doi:10.1021/acs.biochem.7b00211. PMID 28644006. Retrieved 28 August 2020.
  3. ↑ Eiji Yoshihara (18 August 2020). "TXNIP/TBP-2: A Master Regulator for Glucose Homeostasis". Antioxidants. 9 (8): 765–84. doi:10.3390/antiox9080765. PMID 32824669 Check |pmid= value (help). Retrieved 5 September 2020.

External links

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